Study Objective. To compare the erythropoietic responses and tolerability of two recombinant human erythropoietin (EPO) regimens. Design. Prospective, open-label, multicenter study. Setting. Three multidisciplinary intensive care units in Quebec, Canada. Patients. Sixty critically ill patients. Intervention. The first 30 patients received EPO 40,000 U/week (group A); the next 30 received 40,000 U twice/week (group B). Measurements and Main Results. Percent change from baseline in reticulocyte count and hemoglobin concentration were evaluated in both groups on study days 7 and 14. The numbers of adverse events were also compared between the two groups. No statistically significant differences were found in the results between the two groups. Conclusion. Although the study had limitations, it suggested that EPO 40,000 U twice/week did not increase or sustain stimulation of the erythropoietic response compared with EPO 40,000 U/week in critically ill patients.